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Port-wine stains (PWS) are congenital vascular malformations characterized by capillary malformations that persist and often darken over time. Traditional treatment methods, including laser therapy, have shown varying degrees of effectiveness and can be associated with significant side effects. Hematoporphyrin Monomethyl Ether-Photodynamic Therapy (HMME-PDT) has emerged as a promising alternative, offering targeted treatment with potentially fewer adverse effects. This paper aims to evaluate the clinical efficacy and potential of HMME-PDT as a treatment strategy for PWS. It provides a comprehensive review of the literature and clinical investigations to assess the application and outcomes of HMME-PDT in treating PWS. Briefly introduce the nature of PWS, innovations and challenges in treatment, the mechanism of HMME-PDT, clinical effectiveness and sonographic appearance, safety and long-term effects, and challenges and suggestions for optimizing treatment. The review highlights the mechanism by which HMME-PDT works, focusing on its ability to target abnormal blood vessels selectively. Clinical evaluations included clinical and sonographic assessments to determine the efficacy of the treatment. The findings revealed significant improvements in the clinical appearance and sonographic features of vascular lesions following HMME-PDT. The paper also discusses the utility of dermoscopy in HMME-PDT applications, factors affecting treatment efficacy, the impact of thermal assistance on the effectiveness of PDT, and the management of adverse reactions through proper nursing care. The review underscores the considerable potential of HMME-PDT as an effective treatment for PWS, noting its promising outcomes in clinical and sonographic assessments. However, it also emphasizes the need for further research to standardize treatment protocols and assess long-term outcomes., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Despite the promising results in terms of effectiveness of anticancer treatments, a wide range of dermatologic adverse reactions have been reported. Among them, skin photosensitivity, defined as a range of dermatologic conditions caused or exacerbated by sunlight exposure, is an emerging adverse event., Evidence Acquisition: A review of the current literature was performed to report the most characteristic phototoxic and photoallergic reactions associated with anticancer therapies, as well as other characteristic manifestations potentially related to photo-exposure, including UV recall, vitiligo-like reactions, drug-induced cutaneous lupus erythematosus, and UV-induced hyperpigmentation., Evidence Synthesis: A total of 30 manuscripts were collected in the present review, reporting several phototoxic and photoallergic reactions associated with anticancer therapies., Conclusions: Photosensitivity reactions are an increasing challenge in cancer management. The raising awareness about this adverse event has increased the identification of potential photosensitizing drugs as well as its prevention and the management. However, more studies are required to improve the knowledge of this cutaneous toxicity and to define a personalized treatment strategy.

Purpose of Review: 5-Aminolevulinic acid hydrochloride (5-ALA), available under the trade name Gleolan, is an orally administered fluorophore drug used to enhance visual differentiation of cancerous tissue from healthy tissue, primarily during surgical resection of high-grade gliomas. Although given preoperatively, 5-ALA has important implications for anesthetic care throughout the perioperative period. This article reviews pharmacology, safety concerns, and perioperative considerations for patients who receive oral 5-ALA., Recent Findings: Although approved for clinical use by the United States Food and Drug Administration in 2017, studies and case reports published since then have further delineated side effects of this medication and its mechanisms and pharmacokinetics., Summary: Mitigating the possible side effects of 5-ALA requires an understanding of its basic mechanism as well as focused perioperative planning and communication. Administration of this medication may result in nausea, vomiting, photosensitivity, increase in serum concentration of liver enzymes, and hypotension. Patients who receive 5-ALA must be protected from prolonged light exposure during the first 48 h after consumption and administration of other photosensitizing agents should be avoided (Supplemental Video File/Video abstract)., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Intraoperative photodynamic diagnosis (PDD) using 5-aminolevulinic acid (5-ALA) is a widely adopted technique to enhance the extent of resection during high-grade glioma (HGG) surgery. Recent updates to the package insert for 5-ALA in Japan now allow its use in combination with drugs that may induce photosensitivity, such as talaporfin sodium (TS). TS is employed in intraoperative photodynamic therapy (PDT) and has been shown to improve overall survival. The combination of 5-ALA with TS is expected to offer further benefits. However, the safety of this combination had not been established. This study reports on the safety of 5-ALA-PDD with TS-PDT in the treatment of recurrent HGG., Methods: 7 patients with recurrent HGG underwent tumor resection using a combination of 5-ALA-PDD and TS-PDT. The incidence of photosensitivity as an adverse effect associated with 5-ALA and TS was evaluated as described in the package insert. Adverse events were assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0., Results: Tumor-specific fluorescence intensity was strong in 4 cases and weak in 3. Photosensitivity occurred in only 1 patient (14.3%). Three patients exhibited CTCAE grade 1 or 2 abnormal liver function, and 1 patient experienced CTCAE grade 1 γ-GTP elevation. All abnormalities improved during follow-up., Conclusions: The combined use of 5-ALA-PDD and TS-PDT for HGG surgery did not increase the risk of serious adverse events in our study. Further investigations with a larger number of cases are needed for a more accurate assessment of its safety and efficacy., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Darier disease and Hailey-Hailey disease are rare autosomal dominant genodermatoses that negatively impact patient quality of life. In addition, they pose challenges to dermatologists who manage these diseases. There is currently no treatment that reliably induces remission for either disease, leaving patients dependent on symptom management. Oral and topical retinoids are the most commonly used therapies but have numerous side effects that often lead to discontinuation or inability to tolerate long-term treatment (Burge and Wilkinson in J Am Acad Dermatol 27:40-50, 1992). Due to the rarity of these diseases, there are no clinical trials investigating treatment options for the persistent flares patients experience. In light of this, dermatologists have tried various methods used in the management of other inflammatory disorders including photodynamic therapy (PDT). A systematic review was conducted to investigate this treatment option which yielded a total of 12 studies that had reported the use of photodynamic therapy (PDT) as a treatment option for Darier or Hailey-Hailey disease. Though results showed that PDT can induce disease remission for up to several months or years, there are many unanswered questions that need to be addressed before adopting PDT as a leading treatment option for those genodermatoses. In particular, cost, tolerability, and efficacy and safety in patients who are skin of color need to be further studied. Lastly, recommendations on treatment duration, number of sessions, photosensitizing agents, lasers, and continuation or discontinuation of topical and systemic medications need to be appraised before formal recommendations can be made., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Phakomatosis pigmentovascularis (PPV) is a rare congenital syndrome. Only a few studies have reported the treatment of PPV, including a case using photodynamic therapy (PDT) to treat PPV-associated port-wine stains (PWS)., Objective: To investigating the efficacy and adverse effects of hemoporfin-PDT in PPV-associated PWS., Methods: The efficacy and adverse effects in patients with PPV who underwent two sessions of hemoporfin-PDT from January 2019 to December 2022 were retrospectively analyzed., Results: Twenty patients were included (13 females, 7 males, age range: 2-31 years; mean: 8.20 ± 8.92 years). Two, nine, seven, and two patients had PPV types Ia, IIa, IIb, and IIIa, respectively. After two treatments, the visual evaluation indicated the color of the PWS in 4, 5, 6, and 5 patients showed poor, fair, good, and excellent improvements, respectively. The combined good and excellent improvement rates in patients with PWS and pigmentary nevus overlapping in the same treatment area and in patients with PWS in the treatment areas only were 33.3% versus 87.5%, respectively, and were significantly different (p = 0.02). Minor side effects, such as edema, scabbing, hyperpigmentation, and blistering, were observed in some patients after PDT., Conclusion: Hemoporfin-PDT is an effective treatment for PPV-associated PWS. Patients with PWS and pigmentary nevus overlapping in the same treatment area showed poorer efficacy than patients with PWS in the treatment areas only., (© 2024 The Authors. Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Purpose: To evaluate the efficacy and safety of photodynamic therapy (PDT) with chlorin E6 in chronic central serous chorioretinopathy., Methods: In this single-center retrospective cohort study, all patients received standard PDT with 6 mg of chlorin E6 (Fotoran E6) for each m 2 of body surface area with 50 J/cm 2 fluence and a treatment time of 83 seconds. The changes in central retinal thickness, subfoveal choroidal thickness, and best-corrected visual acuity were evaluated at the end of the follow-up. The main outcome measure was the presence of subretinal fluid at 3 months after PDT., Results: Thirty-nine eyes (32 men and 7 women, 43.7 ± 10.0 years) were included. In total, 50 PDT sessions were performed. At 3 months of follow-up, 31 of 39 (79.5%) study eyes showed complete resolution of subretinal fluid. The mean follow-up period after PDT was 15.3 ± 7.8 months. At the end of the follow-up, a complete resolution of subretinal fluid was observed in 32 of 39 (82.7%) eyes. The mean change in central retinal thickness, subfoveal choroidal thickness, and best-corrected visual acuity at the end of the follow-up was -139.7 ± 136.4 µ m, -66.8 ± 36.2 µ m, and -0.05 ± 0.08 logMAR, respectively ( P < 0.001). Neither systemic nor ocular adverse events were observed, nor were local reactions seen., Conclusion: Standard PDT with chlorin E6 is an effective and safe option in the management of chronic central serous chorioretinopathy and may be considered as an alternative to the standard PDT with Visudyne.

Objective: Intraoperative hypotension remains a serious adverse event of photodynamic diagnosis-assisted transurethral resection of bladder tumor with oral administration of 5-aminolevulinic acid. We conducted a re-analysis of perioperative hypotension in photodynamic diagnosis-assisted transurethral resection of the bladder tumor with oral 5-aminolevulinic acid to ascertain its safety., Methods: A total of 407 cases who underwent transurethral resection of bladder tumors in our institution were reviewed (274 cases for the PDD group with photodynamic diagnosis and 133 for the white light (WL) group without). A classification of hypotension severity was devised to identify risk factors for clinically troublesome hypotension. The distribution of hypotension severity in each of the PDD and WL groups was compared. Additionally, the patient background and perioperative data by hypotension severity were compared only in the PDD group., Results: More patients with moderate and severe hypotension were noted in the PDD group. The renal function was lower with increasing hypotension severity in the PDD group. More patients on general anesthesia were included in the mild and moderate hypotension group, whereas more patients on spinal anesthesia were included in the severe hypotension group. Furthermore, the frequency of side effects other than hypotension tended to increase with hypotension severity., Conclusions: Renal function impairment and the other adverse effects of 5-aminolevulinic acid may be risk factors for severe hypotension. Mild or moderate hypotension may be caused by general anesthesia and severe hypotension may be caused by spinal anesthesia. To elucidate specific risk factors, further case-control studies are warranted., (© 2024 The Japanese Urological Association.)

Background: Although 5-aminolevulinic acid is useful for the photodynamic diagnosis of bladder tumors, it often causes severe intraoperative hypotension. We report a case of postoperative cardiac arrest in addition to severe intraoperative hypotension, probably owing to the use of 5-aminolevulinic acid., Case Presentation: An 81-year-old Japanese man was scheduled to undergo transurethral resection of bladder tumor. The patient took 5-aminolevulinic acid orally 2 hours before entering the operating room. After the induction of anesthesia, his blood pressure decreased to 47/33 mmHg. The patient's hypotension did not improve even after noradrenaline was administered. After awakening from anesthesia, the patient's systolic blood pressure increased to approximately 100 mmHg, but approximately 5 hours after returning to the ward, cardiac arrest occurred for approximately 12 seconds., Conclusion: We experienced a case of postoperative cardiac arrest in a patient, probably owing to the use of 5-aminolevulinic acid. Although the cause of cardiac arrest is unknown, perioperative hemodynamic management must be carefully performed in patients taking 5-aminolevulinic acid., (© 2024. The Author(s).)

Background: Peer-reviewed, clinical studies measuring the efficacy and usability of skin care products enhance their integrity and may guide experts in the field in providing recommendations. A single-blind, prospective clinical study was designed to assess the subject satisfaction, clinical benefit, and safety of three photodynamic topical formulations referred to as MMSRepose (MMSRep), MMSRevive (MMSRev), and MMSBalance (MMSB).&nbsp; Methods: Thirteen male and female patients (mean age 49&nbsp;+/- 17.8 years) applied one of the three topical serums twice daily over a period of 12 weeks. Subjects returned for photography, and blinded investigator evaluation of rhytides (fine lines) and dyspigmentation were measured on a 6- and 4-point scale, respectively. Patient-perceived efficacy of multiple clinical outcomes was measured on a 5-point scale.&nbsp; Results: 100% of subjects reported at least a 1-grade improvement in global aesthetic at the conclusion of the study. Investigator assessment revealed an overall 53.3% decrease in rhytides, correlating to a mean point reduction from 1.65 +/- 0.77 to 0.77&nbsp;+/- 0.53 (P&lt;0.001) from baseline to week 12. Investigator assessment of dyspigmentation revealed a 62.7% decrease, correlating to a mean point reduction of 1.85 +/- 0.68 from week 1 to 0.69&nbsp;+/- 0.48 at week 12 (P&lt;0.001)., Conclusion: Photodynamic serums demonstrate clinical efficacy in skin rejuvenation and high user satisfaction. There were no serious adverse events. This study is limited by the inability to randomize to placebo due to the small sample size, as subject retention was heavily impacted by the SARS-CoV-2 pandemic. Future studies may be indicated to undergo comparison with a larger cohort.&nbsp; J Drugs Dermatol. 2024;23(5):332-337. doi:10.36849/JDD.7167.

Field cancerization theory highlights that the skin surrounding actinic keratoses (AK) is also at increased risk for possible malignant transformation; thus, field-directed treatments may both reduce the risk of AK recurrence and potentially reduce the risk of development of cutaneous squamous cell carcinoma (cSCC). Photodynamic therapy (PDT) with either aminolevulinic acid (ALA) or methylaminolevulinate (MAL), as well as topical treatments such as 5-fluorouracil (5-FU), diclofenac gel, piroxicam, imiquimod, and ingenol mebutate, have all shown higher efficacy than vehicle treatments. PDT is widely recognized for its high efficacy; however, concerns for associated pain have driven new studies to begin using alternative illumination and pretreatment techniques, including lasers. Among topical treatments, a combination of 5-FU and salicylic acid (5-FU-SA) has shown to be the most effective but also causes the most adverse reactions. Tirbanibulin, a new topical agent approved for use in 2020, boasts a favorable safety profile in comparison with imiquimod, 5-FU, and diclofenac. Meanwhile, ingenol mebutate is no longer recommended for the treatment of AKs due to concerns for increased risk of cSCC development. Moving forward, an increasing number of studies push for standardization of outcome measures to better predict risk of future cSCC and use of more effective measures of cost to better guide patients. Here, we present an updated and comprehensive narrative review both confirming the efficacy of previously mentioned therapies as well as highlighting new approaches to PDT and discussing the use of lasers and novel topical treatments for treatment of AK., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Rationale: The bullous variant of central serous chorioretinopathy (CSC) is a severe form of chronic CSC. Patients with the bullous variant of CSC have an increased risk of experiencing multiple pigment epithelial detachments (PEDs) and retinal pigment epithelium (RPE) tears. Photodynamic therapy (PDT) is a treatment for the bullous variant of CSC. RPE tear is a possible postoperative complication of PDT for eyes with PEDs. To our knowledge, no cases of giant RPE tears following PDT for the bullous variant of CSC have been reported previously. This case report presents the first instance of a giant RPE tear after half-time PDT for the bullous variant of CSC, accompanied by a series of images depicting the tear development., Patient Concerns: A 63-year-old male patient presented with rapidly deteriorating vision in his left eye over a 3-month period. He also reported a previous episode of vision loss in his right eye 2 years prior. Best-corrected visual acuity (BCVA) in the left eye was 0.2., Diagnosis: The right eye was diagnosed with chronic non-bullous CSC, while the left eye was diagnosed with the bullous variant of CSC with a large PED., Interventions: Half-time PDT was administered to the left eye., Outcomes: One month after half-time PDT, a giant RPE tear exceeding 3 clock-hours in size was confirmed in the lower temporal quadrant of the left eye. Three months after the initial half-time PDT, a second half-time PDT was performed owing to recurrent retinal detachment. Two months after the second half-time PDT, the retinal detachment resolved, and BCVA improved to 0.4, 6 months after the second half-time PDT., Lessons: In cases where the bullous variant of CSC is complicated by extensive PED, clinicians should consider the potential development of a giant RPE tear as a treatment complication., Competing Interests: M Miura received funding support from Santen, Alcon, Altos, and Sandoz, and lecture fees from Santen, Kowa, Senju, and Novartis. All other authors have no funding and conflict of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Simulated daylight photodynamic therapy is a relatively new and potentially less painful alternative to conventional red light photodynamic therapy for actinic keratosis. Qualitative research exploring patient experiences of pain and skin reactions during these treatments is scarce. To address this, semi-structured interviews were conducted of 10 patients aged 60-81 years with symmetrically distributed actinic keratoses 4 weeks after split-face treatment with conventional red light photodynamic therapy and simulated daylight photodynamic therapy. The participants were recruited from an ongoing clinical randomized trial. Interviews (median length 35 min) were conducted between June 2022 and January 2023, audio-recorded, transcribed verbatim, and analysed qualitatively using content analysis, as described by Graneheim and Lundman. Participants reported that conventional red light photodynamic therapy was very painful during illumination and transiently painful in the post-treatment period, while simulated daylight photodynamic therapy was almost painless during illumination and led to minor post-treatment pain. Also, skin reactions were more intense and longer-lasting with conventional red light photodynamic therapy than with simulated daylight photodynamic therapy. Most participants expressed a treatment preference for simulated daylight photodynamic therapy but had reservations about its unestablished long-term effectiveness. This study underscores the considerable pain associated with conventional red light photodynamic therapy, and the pivotal importance of shared decision-making when selecting the most appropriate treatment.

Introduction: Photodynamic therapy (PDT) is a safe, non-mutagenic, and non-scarring treatment for actinic keratoses (AK)., Background: 'Painless' photodynamic therapy (p-PDT) is a regimen for AK that employs simultaneous aminolevulinate incubation and blue light illumination. The efficacy of p-PDT resembles that of traditional PDT, but detailed mechanisms of action for p-PDT are not well understood., Methods: To characterize the inflammatory effects of the p-PDT procedure 48 h following treatment and determine the association of inflammation with precancer burden, we performed a retrospective cohort study of 104 patients with AK of face or scalp treated with p-PDT between 2017 and 2019. Patients self-reported their side effects 48 h following p-PDT and took photographs of their face and scalp. Photographs were edited to define seven anatomic regions, and erythema was scored by four investigators., Results: Ninety-eight patients provided photographs suitable for erythema evaluation. Most patients experienced 2 or more side effects and some pain 48 h post-procedure. Females experienced more pain (p = 0.01) and side effects (p = 0.002) compared to males. AK burden was positively associated with post p-PDT erythema response (p < 0.0001) at all sites, but particularly in the temples (p = 0.002) and supralabial area (p = 0.009)., Discussion: This study confirms a strong clinical inflammatory response after p-PDT. Severity of inflammation is positively associated with AK tumor burden, suggesting that post-treatment inflammation may be a pre-requisite for p-PDT efficacy. Interestingly, the results also identify certain gender-related differences in the severity of side effects experienced by patients post-PDT., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2023. Published by Elsevier B.V.)

This study provides an overview of the effectiveness and safety of PDT for the treatment of HPV-associated precancerous cervical conditions and contains recent findings from relevant research studies. A comprehensive literature search of MEDLINE/PubMed, Cochrane Central Library, and Google Scholar was conducted, including analytic epidemiological studies, and 11 papers were included. The narrative synthesis approach was used to summarize the results of the included studies. Studies were critically appraised using The Joanna Briggs Institute (JBI) tool for assessing the risk of bias. The results of the study demonstrate that CRR for HPV remission ranges from 66.7 % to 92.73 %, whereas for CIN1 it fluctuates from 57.1 % to 83.3 %. The frequency of recurrence of the disease ranged from 3.3 % to 8.9 % during the follow-up period of up to 2 years. Adverse events were observed in 8 (66 %) studies and the most common were cervical stenosis, abdominal pain, vaginal pain, and focal edema. Five types of topical and intravenous applications along with lasers of various wavelengths and intensities were mostly used. However, all studies demonstrated relatively similar results. According to the results, PDT has demonstrated favorable outcomes, but no impressive effect on the treatment of CIN. It should be emphasized, that the effectiveness of PDT for the treatment of HPV-associated CIN may vary depending on some variables, including the kind of PDT agent used, the dosage, duration and frequency of PDT administration, the severity and location of the lesions, and the host immunological response., Competing Interests: Conflict of interest The authors have no conflicts of interest to disclose., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: To describe the incidence, features, and clinical outcomes of photodynamic therapy-induced acute exudative maculopathy (PAEM) in circumscribed choroidal hemangioma., Methods: Prospective series of 10 patients who underwent standard-fluence photodynamic therapy for circumscribed choroidal hemangioma. Best-corrected visual acuity in the Early Treatment Diabetic Retinopathy Score and swept-source optical coherence tomography were performed before PDT and 3 days and 1 month after PDT. Central retinal thickness, circumscribed choroidal hemangioma retinal thickness, and subretinal fluid were measured. Photodynamic therapy-induced acute exudative maculopathy was considered as an increase ≥50 µ m in subretinal fluid or intraretinal fluid or the appearance of fibrin 3 days after photodynamic therapy., Results: Six men and four women were included; median age was 55 years (19-69 years). The incidence rate of PAEM was 7 of 10. Five PAEM patients showed an increase in intraretinal fluid, two in subretinal fluid, and one developed abundant fibrin. Median best-corrected visual acuity at baseline was 57.5 letters (5-76 letters) being stable at 1 month (64 letters; 5-80) ( P = 0.03). Median central retinal thickness increased from 516 µ m (262-1,265 µ m) to 664.5 µ m after 3 days and diminished to 245 µ m after 1 month (156-1,363) ( P ≤ 0.022). In 6 of 7 of PAEM, a complete resolution of the fluid was obtained., Conclusion: Photodynamic therapy-induced acute exudative maculopathy was frequent in circumscribed choroidal hemangioma, although a favorable prognosis was observed in most cases.

Background: Modified 5-aminolevulinic acid photodynamic therapy (M-PDT) and isotretinoin (ISO) are effective treatments for moderate to severe acne vulgaris., Objective: To evaluate the efficacy and adverse effects of M-PDT and ISO for moderate to severe acne vulgaris., Methods: A multicenter, randomized clinical trial was conducted with participants randomly assigned to the M-PDT group (up to 5 weekly sessions following manual comedone extraction) or the ISO group (oral ISO, 0.5 mg/kg/d for 6 months) and followed up to 6-months after therapy., Results: A total of 152 patients were allocated. The overall effective rates in the M-PDT group were significantly higher than the ISO group at 1 month (67.74% vs 10.26%), whereas the opposite was the case 1 month after treatment (75.81% vs 97.44%). Time to achieve 50% lesion improvement in the M-PDT group was significantly less than the ISO group (1 vs 8 weeks). Overall, 70.67% of the ISO group patients experienced systemic side effects such as hepatotoxicity, whereas side effects were skin-limited in the M-PDT group., Limitations: Limitations of this study included relatively low numbers of participants and high withdrawal rate., Conclusion: M-PDT offers a more rapid onset of improvement, comparable overall efficacy, good tolerability, and comparable durability of response compared with ISO., Competing Interests: Conflict of interest None disclosed., (Copyright © 2023 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: To analyze the 2-year clinical outcomes after photodynamic therapy-induced acute exudative maculopathy (PAEM) in patients with chronic central serous chorioretinopathy., Methods: Prospective observational study that included 64 eyes of 64 patients with chronic central serous chorioretinopathy who received half-fluence photodynamic therapy and had a 2-year follow-up. Patients were classified into two groups based on whether they had had PAEM at 3 days after treatment (PAEM+, n = 22; ≥50 µ m) increase in subretinal fluid or not (PAEM-, n = 42). Best-corrected visual acuity and subretinal fluid changes evaluated with optical coherence tomography were registered at 3 days, 1 month, 3 months, 1 year, and 2 years after photodynamic therapy. The number of recurrences, the appearance of outer retinal atrophy, and choroidal neovascularization were analyzed., Results: Best-corrected visual acuity was 75.9 ± 13.6 (20/32) and 82.0 ± 11.0 letters (20/25) at 2 years in the PAEM+ and PAEM- groups, respectively ( P = 0.055). There were no differences in the best-corrected visual acuity change (4.2 ± 7.7 vs. 3.3 ± 7.1 letters; P = 0.654) and the subretinal fluid decrease (-117.3 ± 74.2 vs. -138.5 ± 83.6 µ m; P = 0.323) at 2 years between patients with and without PAEM. No differences in the number of recurrences ( P = 0.267), the appearance of choroidal neovascularization ( P = 0.155), or outer retinal atrophy ( P = 0.273) between both groups were noted., Conclusion: Patients with chronic central serous chorioretinopathy with and without PAEM presented similar results at 2 years in best-corrected visual acuity gain, subretinal fluid reduction, and complication rate.

Background and Aims: Pharmacovigilance reports, associating hydrochlorothiazide (HCT) with skin cancer, resulted in a significant decrease of HCT prescriptions for hypertension and heart failure. Whether HCT exhibits phototoxic properties thereby causing skin cancer remains unknown. This study aimed to examine the photosensitizing, phototoxic and carcinogenic potential of HCT in a randomized, placebo-controlled, double-blind trial in vivo and also in vitro ., Methods: The trial assigned 30 healthy, normotensive adult volunteers in a 2:1 ratio to either HCT 25 mg/day or placebo for 15 days. Photosensitivity of the skin with and without the effect of HCT treatment were assessed. Following whole-body ultraviolet A (UVA) and B (UVB, 311 nm) irradiation, phototoxic and carcinogenic reactions by measuring urinary excretion of pyrimidine dimers were evaluated. For the in-vitro studies, human keratinocytes (HaCaT) were incubated with HCT, irradiated with UVB, and analysed for markers of inflammation, apoptosis and carcinogenesis., Results: Skin photosensitivity following exposure to UVA and UVB remained unchanged from baseline to 15-day follow-up in both groups (UVA change HCT 0.0 J/cm 2 vs. placebo 0.0 J/cm 2 ; P  = 0.99; UVB change HCT 0.0 J/cm 2 vs. placebo -0.2 J/cm 2 ; P  = 0.06). Pyrimidine dimers were not detected in either group. In vitro , combination of HCT and UVB irradiation did not induce the expression of oxidative stress marker proteins, inflammatory proteins, apoptotic proteins or activation of oncoproteins., Conclusion: HCT did not increase photosensitivity for UVA or UVB in healthy volunteers compared with placebo, and was not associated with phototoxic or carcinogenic reactions. In vitro , HCT was also not associated with phototoxicity or carcinogenesis (NCT04654312)., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To evaluate the safety and efficacy of combined simultaneous photorefractive keratectomy (PRK) with collagen cross-linking (CXL) in keratoconus suspects (KCS)., Methods: This was a retrospective, non-randomized study of KCS patients who underwent combined simultaneous PRK with CXL. The efficacy, safety, refractive outcomes, and corneal wavefront aberration changes were assessed after the surgery and compared with existing preoperative data., Results: Fifty-six eyes of 28 patients, including 20 females (71.4%), with a mean age of 30.92±4.09 years, were enrolled. The mean follow-up was 19.46±8.48 months (range: 7-35). At the conclusion of the study, mean uncorrected distance visual acuity LogMAR improved from 0.89±0.44 preoperatively to 0.04±0.09 postoperatively (P<0.001). In addition, a statistically significant corneal flattening was observed postoperatively, with a decrease in manifest refraction. A statistically significant increase was found in higher-order aberrations (P<0.001), horizontal coma (P<0.001), and spherical aberration (P<0.001) compared with preoperatively. Postoperatively, 41% exhibited refractive astigmatism of 0.50 diopter (D) or less; 83.8% showed 1.00 D or less., Conclusion: The results of our study indicate that combined simultaneous PRK with CXL can be a safe and effective method for treating refractive instability in KCS patients., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Background: 5-Aminolevulinic acid photodynamic therapy (ALA-PDT) showed potential to treat rosacea according to recent studies; however, a lack of clinical evidence and unclear adverse effects limit its use., Objective: To compare the effect of ALA-PDT vs minocycline on rosacea., Methods: In this single-center, randomized, evaluator-blind, controlled study, patients with moderate-to-severe rosacea were allocated to receive 3 to 5 sessions of ALA-PDT or 8 weeks of 100 mg daily minocycline treatment, followed by a 24-week follow-up., Results: Of all the 44 randomized patients, 41 received complete treatment (ALA-PDT: 20 and minocycline: 21 patients). At the end of treatment, ALA-PDT showed noninferior improvement of papulopustular lesions and Rosacea-specific Quality of Life compared with minocycline (median reduction of lesion count: 19 vs 22, median change of Rosacea-specific Quality of Life score: 0.48 vs 0.53). The Clinician's Erythema Assessment success of ALA-PDT was lower than that of minocycline's (35% vs 67%). Demodex density and relapse rate were comparable in both groups. Erythema, mild pain, and exudation were the most common adverse reactions of ALA-PDT., Limitations: Limited sample size restricted us from drawing further conclusions., Conclusion: As minocycline does, ALA-PDT can improve rosacea mainly in papulopustular lesions and patients' quality of life, indicating a new option for rosacea., Competing Interests: Conflicts of interest None disclosed., (Copyright © 2023 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Hematoporphyrin monomethyl ether-photodynamic therapy (HMME-PDT) has achieved encouraging clinical outcomes in adult port-wine stain (PWS). Optimal treatment option for children with PWS was minimal. To compare whether the clinical effectiveness of HMME-PDT with the 5-min (fast) administration treatment regimen (FATR) was better than the 20-min (slow) administration treatment regimen (SATR) for PWS of children in vivo and in vitro. Thirty-four children with PWS were divided into two groups including FATR and SATR. The two groups received three times HMME-PDT, respectively. Treatment efficacy and safety were evaluated in vivo and in vitro. Erythema index (EI) was used to evaluate the clinical outcomes. Both FATR and SATR were effective and safe in children with PWS after HMME-PDT. There were significance differences between the two groups in reductions of EI after the second treatment (p < 0.001) and the third treatment (p < 0.001) with HMME-PDT. The serum HMME concentration reach the peak level at short time compare with SATR group. A significance increased superoxide levels were observed in FATR group compare to SATR groups in vitro (p < 0.05). Our study suggested that HMME-PDT was effective and safe for children with PWS, the therapy regimen with FATR was better in clinical efficacy than that of the SATR., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: The efficacy of photodynamic diagnosis using 5-aminolevulinic acid during transurethral resection of bladder tumors has been demonstrated, albeit with limited information regarding its side effects. This study aimed to clarify the impact of oral 5-aminolevulinic acid on perioperative nausea and vomiting (NV) for the first time in a real-world clinical practice setting., Methods: Patients who underwent transurethral surgery at Kagawa University between April 2017 and March 2020 were included. Perioperative NV and antiemetic use status were prospectively assessed and compared between the patients who received oral 5-aminolevulinic acid and those who did not. Additionally, univariate and multivariate analyses were performed for predicting postoperative nausea and vomiting., Results: Of 214 patients, 74 (34.6%) received oral 5-aminolevulinic acid preoperatively. The proportions of preoperative NV and antiemetic use in the patients who received 5-aminolevulinic acid were 9.5% and 4.1%, respectively, and higher than in those who did not (0% and 0%; P < 0.01 and P = 0.04, respectively). Postoperative NV (25.7%) and antiemetics use (8.0%) ratios in the patients who received 5-aminolevulinic acid were significantly different from those in the non-users group (3.6% and 2.1%, P < 0.01 and P < 0.01, respectively). Although no differences in risk factors were found for postoperative NV between the two groups, multivariate analyses indicated 5-aminolevulinic acid use as an independent predictive factor for postoperative NV (odds ratio, 11.5; 95% confidence interval, 3.98-33.3; P < 0.01)., Conclusions: Our study clearly showed that oral administration of 5-aminolevulinic acid was associated with perioperative NV even without risk factors, highlighting the need for addressing its application., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Actinic keratoses (AKs) are common and some may evolve into squamous cell carcinoma. Photodynamic therapy (PDT), imiquimod, cryotherapy, and other methods have been reported to have good effects. However, which treatment is the most effective with the best cosmetic results and fewest complications is uncertain., Objective: To evaluate which method has the best efficacy and cosmetic results with less adverse events and recurrence rate., Materials and Methods: All relevant articles up to July 31, 2022 were searched from Cochrane, Embase, and PubMed databases. Extract and analyze the data of efficacy, cosmetic results, local reactions, and adverse effects., Results: Twenty-nine articles with 3,,850 participants and 24,747 lesions were included. Quality of evidence was generally high. The efficacy of PDT was better in complete response (CR) (lesions CR; risk ratio (RR) 1.87; 95% confidence interval (CI) 1.55-1.87/patient CR; RR 3.07; 95% CI 2.07-4.56), overall preference, and cosmetic results. The time cumulative meta-analysis showed that the curative effect was gradually increasing before 2004, and then gradually stabilizing. Two groups showed no statistically significant differences in recurrence., Conclusion: Compared with other methods, PDT is significantly more effective for AK with excellent cosmetic results and reversible adverse effects., (Copyright © 2023 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Background: To investigate the effectiveness, safety, patient satisfaction, and cosmetic outcome of Methyl Aminolevulinate-Photodynamic Therapy (MAL-PDT) following curettage in order to make recommendations for its use in dermatology practices., Methods: A retrospective chart review of patients who received MAL-PDT following curettage for the indication of basal cell carcinoma (BCC) between 2009 and 2016 at a single private clinic in Ontario, Canada. Two hundred and seventy-eight patients with 352 BCC lesions were included, consisting of 44.2% males (n=123) and 55.8% females (n=155) with a mean age of 57.24 years. The primary outcome measurement consisted of the cure rate. Secondary outcome measurements included side effects, patient satisfaction, and cosmetic outcome, as reported in the medical charts., Results: The overall cure rate was 90.3% (n=318). After controlling for age, sex, and lesion type, nasal lesions were approximately 2.82 (95% CI: 1.24-6.40, P=0.01) times more likely to experience a recurrence. 18.3% of patients (n=51) reported side effects, the most common being burning (n=19). Of those who expressed satisfaction, 100% (n=25) reported being happy. Of lesions with cosmetic data, 90.3% displayed a good response (n=149)., Conclusion: MAL-PDT following curettage is an effective and safe treatment option for BCC lesions with a good cosmetic outcome and suggested high patient satisfaction. J Drugs Dermatol. 2023;22(5): doi:10.36849/JDD.7133.

Background: Patient selection for transurethral resection of the bladder tumor using photodynamic diagnosis (PDD-TURBT) with oral 5-aminolevulinic acid (5-ALA) hydrochloride for non-muscle-invasive bladder cancer (NMIBC) is still unclear as to the best balance of risks (adverse events including hypotension) and benefits (reduction of intravesical recurrence)., Methods: This single-center retrospective study between April 2013 and March 2022, compared the intravesical recurrence-free survival between patients who underwent PDD-TURBT and WL-TURBT using propensity score matching., Results: A total of 222 patients who underwent PDD-TURBT and 177 patients who underwent WL-TURBT for NMIBC were included. Propensity score matching was used to compare intravesical recurrence-free survival in 119 NMIBC patients in the both treatment groups. The intravesical recurrence-free survival within 500 days was significantly higher in the PDD-TURBT group than in the WL-TURBT group (P = 0.039; hazard ratio [HR] 0.48 [0.23-0.98]). Subgroup analysis showed that PDD-TURBT contributed to the reduction of short-term intravesical recurrence in patients aged < 75 years (P = 0.02; HR 0.22 [0.06-0.79]) and primary disease (P = 0.038; HR 0.35 [0.13-0.94]). Hypotension with a systolic blood pressure of < 80 mmHg was observed in 79 patients (35.6%) during PDD-TURBT surgery. In particular, age ≥75 years and general anesthesia were independent prognostic factors for predicting intraoperative hypotension., Conclusions: PDD-TURBT reduced short-term intravesical recurrence in NMIBC, whereas a higher frequency of hypotension was found in patients aged ≥ 75 years. These results suggest that the risks and benefits of PDD-TURBT are well balanced in younger patients (< 75 years) and those with primary disease., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Photodynamic therapy (PDT) is an effective method for treating actinic keratosis (AK) with pain during illumination representing the major side effect. The efficacy of two different cooling methods for pain relief in PDT of AK in the head region was compared., Methods: Randomized, assessor-blinded, half side comparison study in 20 patients with symmetrically distributed AK on the head. Conventional PDT was performed on both halves of the scalp or face by applying 20% aminolevulinic acid cream (ALA) and subsequent illumination with incoherent red light. During illumination one side was cooled with a cold air blower (CAB) and the other with a standard fan (FAN) in a randomized fashion. Pain and skin temperature were recorded during and after PDT. The phototoxic skin reaction was evaluated up to seven days after PDT. The clearance rate of AK was assessed at 3 and 6 months after PDT., Results: Mean pain (VASmean), maximum pain intensity (VASmax) and the mean skin temperature during PDT were significantly lower with CAB as compared to FAN (VASmean: 2.7 ± 1.4 vs. 3.7 ± 2.1, p = 0.003; VASmax: 3.8 ± 2.0 vs. 4.8 ± 2.5, p = 0.002; 26.8 ± 2.0 °C vs. 32.1 ± 1.7 °C; p=<0.001). The severity of the phototoxic skin reaction and the clearance rate of AK did not differ between the two cooling methods., Conclusion: Cooling with CAB during PDT has a greater analgesic effect than cooling with FAN. Patients with a lower skin temperature during illumination tended to experience less pain, however, this effect did not reach the level of statistical significance., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022. Published by Elsevier B.V.)

Background/aim: Actinic keratoses (AKs) are precursors of squamous cell carcinomas and early intervention is important. Photodynamic therapy (PDT) is often first-choice treatment for widespread AKs. Classic PDT consists of: Superficial curettage, application of 5-aminolevulinic acid or methyl aminolevulinate, incubation and protoporphyrin IX (PpIX) accumulation under occlusion for 3 hours, followed by illumination with red light-emitting diode light (37 J/cm 2 ). Classic PDT is effective in treating AKs, but side-effects include unpleasant pretreatment, severe pain during illumination, inflammation after treatment, and long waiting time in the clinic., Materials and Methods: This targeted mini review describes efforts to counteract side-effects and simplify the procedure considering the clinic capacity. Changes are only acceptable if treatment effect is maintained., Results: We introduce the following procedure changes: (i) reducing pre-treatment pain, bleeding, and oozing by omitting curettage; (ii) long-term illumination for 2 hours during PpIX formation (already in use as daylight PDT) and shortening of incubation time from 3 hours to 30 minutes to minimize pain and inflammation risk. In addition, options of timing, incubation, and illumination indoors and outdoors are discussed, focusing on advantages and disadvantages for patients and clinics., Conclusion: We report several options to counteract side-effects of classic PDT., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Conventional photodynamic therapy (c-PDT) is a highly effective treatment for actinic keratoses. Besides pain as the main side effect, blood pressure (BP) increases and hypertensive crises may occur during treatment. Reducing the irradiation intensity while keeping the total dose constant (low-irradiance PDT) can achieve a clinically relevant reduction in pain. This study aimed to evaluate the influence of li-PDT on the BP and pulse (PR) during therapy and the incidence of post-interventional hypertension compared with c-PDT., Methods: We retrospectively analyzed the treatment data of 79 patients (39 c-PDT and 40 li-PDT). BP and PR measurements were performed in all patients before PDT, at mid-exposure, and immediately after PDT. In addition, the pain was assessed by using the visual analog scale., Results: Patients treated with li-PDT reported significantly lower pain than those receiving c-PDT (p < .0005). Additionally, they showed less systolic (SBP) and diastolic (DBP) BP increase (∆SBP: p < .0005, ∆DBP: p = .015) and overall lower absolute BP values (SBP: p < .0005, DBP: p = .008) compared with c-PDT. They were also significantly less likely to develop post-interventional hypertension (p = .037) or higher stages of arterial hypertension. Regarding PR, there was no difference in absolute values between both groups, but the increase from onset to half irradiation duration was significantly higher in c-PDT (p = .013)., Conclusions: Li-PDT is an excellent option to reduce the elevation of arterial BP and decrease the incidence of post-interventional hypertension and hypertensive crisis. This finding has considerable relevance, especially with the risk profile of many PDT patients in mind (advanced age and cardiovascular history)., (© 2021 The Authors. Photodermatology, Photoimmunology & Photomedicine published by John Wiley & Sons Ltd.)

Purpose: To evaluate the use of photodynamic therapy (PDT) with chlorin e6 (Ce6) derivative in patients with chronic central serous chorioretinopathy (CSC). Methods: Participants in this interventional, single-center clinical pilot study included 39 patients (39 eyes) with chronic CSC. Primary objectives were to assess safety and change in decimal best-corrected visual acuity (BCVA) during the 12-month follow-up. Secondary objectives were to evaluate change in central retinal thickness (CRT) in fovea area, maximal height of subretinal fluid (SRF), subfoveal choroidal thickness (SFCT) on spectral-domain optical coherence tomography, and number of treatments. Results: There were no systemic adverse events and ocular side effects. Mean decimal BCVA showed a significant increase from 0.49 ± 0.25 to 0.63 ± 0.28 ( P  = 0.001), mean CRT and maximal height of SRF decreased significantly from 335 ± 95 to 219 ± 69 μm and from 149 ± 84 to 32 ± 86 μm respectively ( P  = 0.001), comparing baseline and month 12. There was no significant difference between mean SFCT before PDT and at month 12. During all follow-up periods mean number of PDT treatments was 1.3 ± 0.7. Complete SRF resolution was observed in 82% (32 eyes) during observation period. Conclusion: Results of this pilot study demonstrate that PDT with Ce6 derivative is a safe method to treat eyes with chronic CSC. PDT with Ce6 derivative is the treatment option for chronic CSC. Further randomized controlled studies with a larger sample size and longer periods of follow-up are needed to assess the effectivity and safety of PDT with Ce6 derivative in chronic CSC.

Classic photodynamic therapy (PDT) is an effective, but painful, treatment of actinic keratosis (AK). Daylight PDT with simultaneous activation of protoporphyrin IX during its formation is almost painless and as effective. Recent studies suggest that this gentle simultaneous activation can be performed indoors by replacing daylight with a suitable light source. We aimed to systematically review efficacy and tolerability of indoor gentle PDT of AKs using various light sources. We systematically searched MEDLINE, Embase, and the Cochrane Library for clinical studies of treatment efficacy or adverse events. Indoor gentle PDT consists of application of methyl aminolevulinate or 5-aminolevulinic acid on the skin prior to long time illumination, starting no later than one hour after application. Fifteen studies met the selection criteria, enrolling 518 patients with more than 5,000 AKs undergoing indoor gentle PDT. The studies mainly included thin AKs comprised of 8 uncontrolled studies and 7 randomized controlled trials (RCT) of which 3 were designed as non-inferiority RCTs. Results from both controlled and uncontrolled trials indicated good treatment tolerability with very low pain scores like those of daylight PDT. Reduction of AK lesions 3 months after indoor gentle PDT in RCTs ranged from 52% to 79%, which is comparable to classic and daylight PDT. All 3 non-inferiority RCTs reported that indoor gentle PDT was non-inferior in terms of efficacy to classic PDT. The included studies used varying treatment protocols with different pretreatments, incubation time, light sources, and irradiation time. No standard protocol for indoor gentle PDT exists yet., Competing Interests: Declaration of Competing Interest None to declare., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Importance: Given that mycosis fungoides-cutaneous T-cell lymphoma (MF/CTCL) is chronic, there is a need for additional therapies with minimal short- and long-term adverse effects. Topical synthetic hypericin ointment, 0.25%, activated with visible light is a novel, nonmutagenic photodynamic therapy (PDT)., Objectives: To determine the efficacy and safety of topical synthetic hypericin ointment, 0.25%, activated with visible light as a nonmutagenic PDT in early-stage MF/CTCL., Design, Settings, and Participants: This was a multicenter, placebo-controlled, double-blinded, phase 3 randomized clinical trial (FLASH study) conducted from December 2015 to November 2020 at 39 academic and community-based US medical centers. Participants were adults (≥18 years) with early-stage (IA-IIA) MF/CTCL., Interventions: In cycle 1, patients were randomized 2:1 to receive hypericin or placebo to 3 index lesions twice weekly for 6 weeks. In cycle 2, all patients received the active drug for 6 weeks to index lesions. In cycle 3 (optional), both index and additional lesions received active drug for 6 weeks., Main Outcomes and Measures: The primary end point was index lesion response rate (ILRR), defined as 50% or greater improvement in modified Composite Assessment of Index Lesion Severity (mCAILS) score from baseline after 6 weeks of therapy for cycle 1. For cycles 2 and 3, open label response rates were secondary end points. Adverse events (AEs) were assessed at each treatment visit, after each cycle, and then monthly for 6 months. Data analyses were performed on December 21, 2020., Results: The study population comprised 169 patients (mean [SD] age, 58.4 [16.0] years; 96 [57.8%] men; 120 [72.3%] White individuals) with early-stage MF/CTCL. After 6 weeks of treatment, hypericin PDT was more effective than placebo (cycle 1 ILRR, 16% vs 4%; P = .04). The ILRR increased to 40% in patients who received 2 cycles of hypericin PDT (P < .001 vs cycle 1 hypericin) and to 49% after 3 cycles (P < .001 vs cycle 1 hypericin). Significant clinical responses were observed in both patch and plaque type lesions and were similar regardless of age, sex, race, stage IA vs IB, time since diagnosis, and number of prior therapies. The most common treatment-related AEs were mild local skin (13.5%-17.3% across cycles 1-3 vs 10.5% for placebo in cycle 1) and application-site reactions (3.2%-6.9% across cycles 1-3 vs 4% for placebo in cycle 1). No drug-related serious AEs occurred., Conclusion and Relevance: The findings of this randomized clinical trial indicate that synthetic hypericin PDT is effective in early-stage patch and plaque MF/CTCL and has a favorable safety profile., Trial Registration: ClinicalTrials.gov Identifier: NCT02448381.

Background: Photodynamic therapy (PDT) has become one of the most effective therapies for the treatment of actinic keratosis, allowing the removal of more than one lesion in a single session. However, the pain sustained by the patient during treatment and local skin reactions can limit its use., Objectives: To determine the efficacy and safety of combined PDT (daylight PDT followed by conventional PDT) vs conventional PDT 12 weeks after treatment., Methods: The study was performed as a randomized, single-center, non-inferiority clinical trial with two parallel groups. A total of 51 patients with grade I and II AKs on the scalp or face were randomized. Twenty-five patients received one session of combined PDT (combPDT), and 26 patients received one session of conventional PDT (cPDT). The primary endpoint was the reduction of AKs, 12 weeks after treatment. The secondary endpoint was the reduction in pain and local skin reaction., Results: The reduction rate of grade I and II AKs was similar in combPDT and cPDT, showing no statistically significant differences between both groups, 76.67% vs 86.63% [P = .094] and 80.48% vs 83.08% [P = .679], respectively. However, pain was significantly lower in the combPDT group (2.56 vs 5, P < .01), as were local skin reactions., Conclusions: CombPDT has proven to be as effective as cPDT for the treatment of grade I and II AKs located on the scalp and face. Furthermore, combPDT has been shown to be considerably more tolerable than cPDT, causing only mild local skin reactions., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

This systemic review aims to provide a practical overview of the prevalence, clinical manifestation, and management of adverse photoinduced skin reactions caused by frequently used cardiovascular drugs and to assess their potential relevance for skin cancer development. Data search included PubMed, Web of Science, and the Cochrane Library. A systematic review of peer-reviewed studies reporting the photosensitizing and/or skin cancer-inducing properties of common cardiovascular drugs was performed and a guide to clinical management of photoinduced skin eruptions by cardiovascular drugs was provided. Study quality was assessed for major methodological biases. A total of 58 studies were identified (i.e. 23 case reports, 14 observational studies, 10 review articles, 10 experimental studies, and 1 meta-analysis). Most commonly, drug-associated adverse photoinduced cutaneous reactions were caused by phototoxic and photoallergic mechanisms. There is evidence suggesting that amiodarone and dronedarone, thiazide diuretics, thiazide-like diuretics, angiotensin receptor blockers, dihydropyridine-type calcium channel blockers, and certain angiotensin-converting enzyme inhibitors and statins may cause photoinduced adverse cutaneous reactions. Other drugs such as anticoagulants, antiplatelets, aldosterone antagonists, and fibrates have not been linked with photosensitizing reactions or adverse cutaneous reactions. Some drugs, i.e. thiazides and thiazide-like diuretics, were associated with an increased risk of non-melanoma skin cancers (basal cell carcinoma and squamous cell carcinoma). Certain commonly used cardiovascular drugs have been associated with adverse photoinduced cutaneous reactions. If they occur, further diagnosis and treatment might be needed, depending on the severity and progress. Whether photosensitizing drugs increase the risk of skin cancer remains elusive and further randomized controlled trials are required., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Backgrounds/aim: Photodynamic therapy (PDT) with Talaporfin sodium (Talaporfin) is an effective and safe treatment for central-type early-stage lung cancer (CELC) that is associated with less skin photosensitivity. However, PDT is mostly performed in hospital for the purpose of light shading management in Japan. It is expected that it will be possible to perform PDT with Talaporfin (Talaporfin-PDT) as a day treatment with ≥14 days of shading management at home. This study aimed to confirm the safety of Talaporfin-PDT as day treatment., Methods: We retrospectively investigated the occurrence of adverse events among consecutive patients who received PDT for CELC in a day treatment setting in the Respiratory Endoscopy Division of our institution between January 2010 and February 2020., Results: A total of 12 patients (16 treatments) received day treatment of Talaporfin-PDT. Among the 12 patients, one patient (one treatment) was followed at another hospital. No severe adverse events after treatment were observed among the remaining 11 patients (15 treatments). Mild photosensitivity on a photosensitivity test was observed in 3 (3 treatments) of the 11 patients (15 treatments) but no major photosensitivity was observed. This photosensitivity was a temporary reaction., Conclusion: Talaporfin-PDT for CELC was safely performed as a day treatment., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Photodynamic therapy (PDT) has gradually developed into a promising modality for actinic cheilitis (AC), and many new PDT strategies are emerging. However, comprehensive reviews evaluating the efficacy of PDT strategies for AC are lacking., Objective: To systematically review the safety and efficacy of PDT strategies for AC., Methods: A systematic review was conducted using three databases to compare several types of PDT for AC in terms of clinical response (CR), histopathology response (HR), cosmetic result, and adverse events., Results: A total of 19 studies were included, and 292 subjects were finally enrolled. The complete CR rate of ALA-patch PDT, traditional photodynamic therapy (T-PDT), and daylight photodynamic therapy (DL-PDT) was 80.00% (24/30), 65.14% (114/179), and 76.74% (33/43), respectively. The rate of painless patients was 87.10% (27/31) in DL-PDT, whereas the rate was only 31.25% (15/48) in T-PDT. The rates of moderate and severe local phototoxicity were 47.78% (43/90) in T-PDT, 0.00% (0/23) in DL-PDT, and 21.05% (4/19) in ALA-patch PDT., Conclusion: Published literature suggests that ALA-patch PDT seem to achieve high complete CR rate. Besides, DL-PDT might be a well-tolerated therapy compared with T-PDT and ALA-patch PDT. However, these assumptions are made based on very limited data. It is necessary to conduct a long-term larger sample randomized controlled trial to further evaluate the efficacy and adverse events of various PDT schemes for AC., (Copyright © 2022. Published by Elsevier B.V.)

Competing Interests: Conflicts of interest None disclosed.

Background: 5-Aminolaevulinic acid photodynamic therapy (ALA-PDT) is an effective therapy for cutaneous diseases, such as precancers, superficial non melanoma skin cancers and certain inflammatory or viral conditions. However, the absence of a complete picture of adverse reactions limits the promotion of ALA-PDT., Objective: To systemically investigate the detailed evidence of adverse reactions relating to ALA-PDT for skin diseases., Methods: A retrospective study performed at the Shanghai Skin Disease Hospital., Results: In the retrospective study, 439 patients were included. Incidences of adverse reactions, including in-treatment pain (98.8%), erythema (92.4%), edema (35.0%), exudation (23.0%), hyperpigmentation (27.3%) were clarified. Edema was more common in female patients (P<0.05). Patients with HPV-related skin diseases were more likely to suffer erythema, edema or exudation (P<0.05). Hyperpigmentation was more likely to occur in skin appendage disorders (P<0.05). Fever (2.4%) and hypopigmentation (1.9%) are two neglected adverse reactions analyzed in detail. Fever is more prevalent in female patients. Hypopigmentation occurred predominantly in elderly with skin cancer or precancerosis lesions., Conclusion: The results outline detailed information about the adverse reactions, including systemic reactions following ALA-PDT, assisting dermatologists in predicting and managing adverse reactions for greater efficacy and higher patient satisfaction., (Copyright © 2022. Published by Elsevier B.V.)

Background: Acne vulgaris is a chronic inflammatory skin disease around pilosebaceous unit. 5-Aminolaevulinic acid photodynamic therapy (ALA-PDT) is an effective therapy for severe acne vulgaris. However, the lack of detailed information of adverse reactions limits the promotion of ALA-PDT in clinic., Objective: To systemically investigate the adverse reactions relating to ALA-PDT for acne vulgaris., Methods: A prospective study was performed at the Shanghai Skin Disease Hospital., Results: In the prospective study, 35 patients with acne vulgaris completed the trial. The adverse reactions were first divided into acute-phase adverse reactions, including erythema (94.3%), post-treatment pain (91.4%), burning skin (91.4%), dry skin (91.4%), itching (85.7%), pustule (82.9%), edema (20%) and blister (11.4%), or recovery-phase adverse reactions, which included crust (65.6%), exudation (48.6%) and hyperpigmentation (42.7%). Younger patients were more likely to have pustules (P<0.05). Male patients were represented itching more often than female patients (P<0.05). The efficacy of ALA-PDT for severe acne was positively related to the severity of acute-phase adverse reactions. The duration of pain was shortest. Crusting and hyperpigmentation lasted considerably longer., Conclusion: In the present study, we recorded the relative incidence of various adverse reactions following ALA-PDT for acne vulgaris. The severity of adverse reactions tended to decrease with increased patient age, except for itching and hyperpigmentation. Light-to-moderate adverse reactions might be the inflammatory reactions of ALA-PDT, predicting a good efficacy. A form for evaluation of adverse reactions based on the present study could assist dermatologists in predicting and managing adverse reactions for greater efficacy and higher patient satisfaction., (Copyright © 2022. Published by Elsevier B.V.)

Purpose: To describe the incidence and characteristics of photodynamic therapy-induced acute exudative maculopathy (PAEM) and bacillary layer detachment in patients with chronic central serous chorioretinopathy., Methods: This was a prospective observational case series including 92 eyes of 75 patients who underwent photodynamic therapy. Best-corrected visual acuity, optical coherence tomography, and optical coherence tomography angiography were performed before, 3 days, 1 month, and 3 months after half-fluence photodynamic therapy. Two groups were established depending on the presence or absence (N = 28 and N = 64, respectively) of PAEM. Choriocapillaris flow voids increase, subfoveal choroidal thickness, and the presence of choroidal neovascularization were collected., Results: The incidence of PAEM was 28/92 (30.4%). There was no difference in the age, sex, baseline subretinal fluid, subfoveal choroidal thickness, or the presence of choroidal neovascularization between groups (P ≥ 0.094). No differences emerged in the subretinal fluid at 1 and 3 months after photodynamic therapy between groups (P ≥ 0.524), nor in the mean best-corrected visual acuity gain at 3 months (4.1 ± 7.6 vs. 3.6 ± 6.4 letters; P = 0.773). A bacillary layer detachment was observed in 13 patients with PAEM (46.4%)., Conclusion: Photodynamic therapy-induced acute exudative maculopathy is frequent in patients with chronic central serous chorioretinopathy but has a favorable prognosis. There was no association between PAEM and age, sex, subfoveal choroidal thickness, or choroidal neovascularization; however, it was related to choriocapillaris flow voids increase.

Corticosteroid-induced central serous chorioretinopathy (CSCR) has been reported to develop in many intraocular inflammatory diseases and usually resolves spontaneously after discontinuation of corticosteroids. Patients without any improvement may require alternative therapies. In this case report, we present the case of a 35-year-old man with Behçet's disease who had complaints of decreased vision due to CSCR in his left eye while using systemic corticosteroids along with cyclosporine and azathioprine. Half-fluence photodynamic therapy (PDT) was performed because the CSCR did not regress despite discontinuation of systemic corticosteroids. After treatment, his visual acuity increased with complete resolution of the subfoveal fluid. Half-fluence PDT seems to be an effective and safe treatment for patients who develop acute CSCR while under systemic or local corticosteroid therapy for intraocular inflammatory diseases such as Behçet's uveitis and do not improve despite steroid discontinuation., Competing Interests: Conflict of Interest: No conflict of interest was declared by the authors., (©Copyright 2022 by Turkish Ophthalmological Association, Turkish Journal of Ophthalmology, published by Galenos Publishing House.)

Pain and inferior efficacy are major limiting factors of conventional photodynamic therapy for the field treatment of actinic keratoses in immunosuppressed organ transplant recipients. This prospective randomized controlled study evaluates the efficacy and tolerability of ablative fractional laser system pretreatment combined with low-irradiance photodynamic therapy (18.5 mW/cm2) compared with conventional photodynamic therapy (61.67 mW/cm2) in the treatment of actinic keratoses on the face and scalp in organ transplant recipients, using a red light-emitting diode lamp at a total light dose of 37 J/cm2. Low-irradiance photodynamic therapy combined with Er:YAG pretreatment achieved a significantly superior lesion response rate (mean ± standard deviation 77.3 ± 23.6%) compared with conventional photodynamic therapy (61.8 ± 21.4%; p = 0.025) in intra-individual fields at 3 months without negatively impacting pain (p = 0.777) or cosmetic outcome (p = 0.157).

Ruta is a common plant growing in Italy and in the Mediterranean area. It has been used in popular tradition with different aims, ranging from therapeutic to esoteric purposes. However, the plant is still used as a common remedy in some of present-day rural and urban communities and it can be found in gardens all over Europe. Ruta's photosensitizing effect has been described in the literature and seems to be mediated by furanocoumarins. We collected data from the 18 case-reports for a total of 32 patients that we included in our analysis, assessing demographic variables, clinical findings, diagnosis, time of onset of lesions, time of resolution and therapy. The main aim of this work was to outline the clinical presentation, therapeutic management and demography of phytophototoxic reactions from contact with Ruta in order to suggest the correct diagnostic approach and disease recognition, as well as its possible prevention.

Competing Interests: The authors declare that they have no conflict of interest.

The nanoemulsion-based 10% aminolevulinic acid (ALA) hydrochloride gel BF-200 ALA optimizes epidermal penetration of its active ingredient and is approved for topical photodynamic therapy (PDT) for the treatment of actinic keratosis in the United States and Europe. To characterize systemic absorption from dermal application during PDT, ALA and its key active metabolite protoporphyrin IX (PpIX) were analyzed in 2 maximal usage pharmacokinetic trials (MUsT) in patients severely affected with actinic keratosis. The primary objective of both MUsTs was to assess baseline-adjusted plasma concentration-time curves for ALA and PpIX after a single PDT treatment applying either 2 g (1 tube) of BF-200 ALA on the face (MUsT-1) or applying 6 g (3 tubes) of BF-200 ALA on the face/scalp or body periphery (MUsT-2), to 20 or 60 cm 2 , respectively. All PDTs were performed using red light at around 635 nm wavelength. Safety and tolerability were documented along with pharmacokinetics. In both MUsTs, ALA plasma concentrations were transiently increased to a maximum concentration at about 2.5 to 3.3 times above endogenous baseline with time to maximum concentration at ≈3 hours after dosing. Plasma levels subsequently returned to baseline within 10 hours after dosing. Overall baseline-adjusted mean area under the baseline-adjusted plasma concentration-time curve from time zero to the last sampling time point at which the concentration was at or above the lower limit of quantification ranged from 142.8 to 146.2, indicating that a similar, minor fraction of topical ALA is systemically absorbed under both dosing regimens. Systemic PpIX exposure after administration of either dose of BF-200 ALA was equally minimal. Application site skin reactions were treatment area size-related, albeit transient and consistent with the known safety profile of BF-200 ALA., (© 2021 The Authors. Clinical Pharmacology in Drug Development published by Wiley Periodicals LLC on behalf of American College of Clinical Pharmacology.)

Background: Pain is a frequent adverse event during photodynamic therapy, which can limit treatment acceptance. This study aimed to evaluate the efficacy and pain during photodynamic therapy with two irradiation protocols in patients with actinic keratosis on the face and scalp., Methods: In this intra-patient randomized controlled trial, participants were randomly allocated to receive photodynamic therapy with methyl aminolevulinate and red light on the right or left side with protocol 1 (irradiation device in contact with the skin) and protocol 2 (device 3 cm away from the skin). There was a 15-day interval between the protocols. The primary outcome was the frequency of mean intensity of moderate or severe pain during photodynamic therapy. Secondary outcomes were actinic keratosis clearance rate, protoporphyrin IX consumption, participant preference, skin appearance, and adverse events., Results: Forty-one participants were included, yielding 47 and 50 randomized sites for protocols 1 and 2. There was no difference in the frequency of moderate and severe pain, with a relative risk of 1.09 (95% CI 0.70-1.70), p>0.05. An actinic keratosis count reduction >60% was observed in both protocols (p<0.01), with no difference between them. There was no difference in protoporphyrin IX consumption. Most treated sites were of good to excellent quality. There was a greater patient preference for protocol 2 (p<0.01)., Conclusions: The pain intensity was similar between the protocols, and the protocols were equally effective for actinic keratosis clearance, protoporphyrin IX consumption, and improvement in the quality of the treated areas. Both protocols may be considered safe., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Competing Interests: The authors have no funding or conflicts of interest to declare.